Short-term effects of obesity surgery versus low-energy diet on body composition and tissue-specific glucose uptake: a randomised clinical study using whole-body integrated 18F-FDG-PET/MRI.

AIMS/HYPOTHESIS: Obesity surgery (OS) and diet-induced weight loss rapidly improve insulin resistance. We aim to investigate the impact of either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with a diet low in energy (low-calorie diet; LCD) on body composition, glucose control and insulin sensitivity, assessed both at the global and tissue-specific level in individuals with obesity but not diabetes. METHODS: In this parallel group randomised controlled trial, patients on a waiting list for OS were randomised (no blinding, sealed envelopes) to either undergo surgery directly or undergo an LCD before surgery. At baseline and 4 weeks after surgery (n=15, 11 RYGB and 4 SG) or 4 weeks after the start of LCD (n=9), investigations were carried out, including an OGTT and hyperinsulinaemic-euglycaemic clamps during which concomitant simultaneous whole-body [18F]fluorodeoxyglucose-positron emission tomography (PET)/MRI was performed. The primary outcome was HOMA-IR change. RESULTS: One month after bariatric surgery and initiation of LCD, both treatments induced similar reductions in body weight (mean ± SD: -7.7±1.4 kg and -7.4±2.2 kg, respectively), adipose tissue volume (7%) and liver fat content (2% units). HOMA-IR, a main endpoint, was significantly reduced following OS (-26.3% [95% CI -49.5, -3.0], p=0.009) and non-significantly following LCD (-20.9% [95% CI -58.2, 16.5). For both groups, there were similar reductions in triglycerides and LDL-cholesterol. Fasting plasma glucose and insulin were also significantly reduced only following OS. There was an increase in glucose AUC in response to an OGTT in the OS group (by 20%) but not in the LCD group. During hyperinsulinaemia, only the OS group showed a significantly increased PET-derived glucose uptake rate in skeletal muscle but a reduced uptake in the heart and abdominal adipose tissue. Both liver and brain glucose uptake rates were unchanged after surgery or LCD. Whole-body glucose disposal and endogenous glucose production were not significantly affected. CONCLUSIONS/INTERPRETATION: The short-term metabolic effects seen 4 weeks after OS are not explained by loss of body fat alone. Thus OS, but not LCD, led to reductions in fasting plasma glucose and insulin resistance as well as to distinct changes in insulin-stimulated glucose fluxes to different tissues. Such effects may contribute to the prevention or reversal of type 2 diabetes following OS. Moreover, the full effects on whole-body insulin resistance and plasma glucose require a longer time than 4 weeks. TRIAL REGISTRATION: ClinicalTrials.gov NCT02988011 FUNDING: This work was supported by AstraZeneca R&D, the Swedish Diabetes Foundation, the European Union's Horizon Europe Research project PAS GRAS, the European Commission via the Marie Sklodowska Curie Innovative Training Network TREATMENT, EXODIAB, the Family Ernfors Foundation, the P.O. Zetterling Foundation, Novo Nordisk Foundation, the Agnes and Mac Rudberg Foundation and the Uppsala University Hospital ALF grants.

Left-ventricular volumes and ejection fraction from cardiac ECG-gated 15O-water positron emission tomography compared to cardiac magnetic resonance imaging using simultaneous hybrid PET/MR.

BACKGROUND: 15O-water PET is the gold standard for noninvasive quantification of myocardial blood flow. In addition to evaluation of ischemia, the assessment of cardiac function and remodeling is important in all cardiac diseases. However, since 15O-water is freely diffusible and standard uptake images show little contrast between the myocardium and blood pool, the assessment of left-ventricular (LV) volumes and ejection fraction (EF) is challenging. Therefore, the aim of the present study was to investigate the feasibility of calculating LV volumes and EF from first-pass analysis of 15O-water PET, by comparison with cardiac magnetic resonance imaging (CMR) using a hybrid PET/MR scanner. METHODS: Twenty-four patients with known or suspected CAD underwent a simultaneous ECG-gated cardiac PET/MR scan. The 15O-water first-pass images (0-50 seconds) were analyzed using the CarPET software and the CMR images were analyzed using the software Segment, for LV volumes and EF calculations. The LV volumes and EF were compared using correlation and Bland-Altman analysis. In addition, inter- and intra-observer variability of LV volumes and EF were assessed for both modalities. RESULTS: The correlation between PET and CMR was strong for volumes (r > 0.84) and moderate for EF (r = 0.52), where the moderate correlation for EF was partly due to the small range of EF values. Agreement was high for all parameters, with a slight overestimation of PET values for end-diastolic volume but with no significant mean bias for other parameters. Inter- and intra-observer agreement of volumes was high and comparable between PET and CMR. For EF, inter-observer agreement was higher for PET and intra-observer agreement was higher for CMR. CONCLUSION: LV volumes and EF can be calculated by first-pass analysis of a 15O-water PET scan with high accuracy and comparable precision as with CMR.

Quantitative comparison of data-driven gating and external hardware gating for 18F-FDG PET-MRI in patients with esophageal tumors.

BACKGROUND: Respiratory motion during PET imaging reduces image quality. Data-driven gating (DDG) based on principal component analysis (PCA) can be used to identify respiratory signals. The use of DDG, without need for external devices, would greatly increase the feasibility of using respiratory gating in a routine clinical setting. The objective of this study was to evaluate data-driven gating in relation to external hardware gating and regular static image acquisition on PET-MRI data with respect to SUVmax and lesion volumes. METHODS: Sixteen patients with esophageal or gastroesophageal cancer (Siewert I and II) underwent a 6-min PET scan on a Signa PET-MRI system (GE Healthcare) 1.5-2 h after injection of 4 MBq/kg 18F-FDG. External hardware gating was done using a respiratory bellow device, and DDG was performed using MotionFree (GE Healthcare). The DDG raw data files and the external hardware-gating raw files were created on a Matlab-based toolbox from the whole 6-min scan LIST-file. For comparison, two 3-min static raw files were created for each patient. Images were reconstructed using TF-OSEM with resolution recovery with 2 iterations, 28 subsets, and 3-mm post filter. SUVmax and lesion volume were measured in all visible lesions, and noise level was measured in the liver. Paired t-test, linear regression, Pearson correlation, and Bland-Altman analysis were used to investigate difference, correlation, and agreement between the methods. RESULTS: A total number of 30 lesions were included in the study. No significant differences between DDG and external hardware-gating SUVmax or lesion volumes were found, but the noise level was significantly reduced in the DDG images. Both DDG and external hardware gating demonstrated significantly higher SUVmax (9.4% for DDG, 10.3% for external hardware gating) and smaller lesion volume (- 5.4% for DDG, - 6.6% for external gating) in comparison with non-gated static images. CONCLUSIONS: Data-driven gating with MotionFree for PET-MRI performed similar to external device gating for esophageal lesions with respect to SUVmax and lesion volume. Both gating methods significantly increased the SUVmax and reduced the lesion volume in comparison with non-gated static acquisition. DDG resulted in reduced image noise compared to external device gating and static images.

Effects of Gastric Bypass Surgery on the Brain: Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia.

While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by 18F-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.

Longitudinal changes in myocardial T1 and T2 relaxation times related to diffuse myocardial fibrosis in aortic stenosis; before and after aortic valve replacement.

BACKGROUND: Diffuse myocardial fibrosis is associated with adverse outcomes, although detection and quantification is challenging. Cardiac MR relaxation times mapping represents a promising imaging biomarker for diffuse myocardial fibrosis. PURPOSE: To investigate whether relaxation times can detect longitudinal changes in myocardial tissue composition associated with diffuse fibrosis in patients with severe aortic stenosis (AS) before and after aortic valve replacement (AVR). STUDY TYPE: Prospective longitudinal study. POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL: Fifteen patients with severe AS. FIELD STRENGTH/SEQUENCE: 3T / 3(3)3(3)5-MOLLI, T2 -GraSE, and 3D-QALAS. ASSESSMENT: Patients underwent MR examinations at three timepoints: before AVR, as well as 3 and 12 months after AVR. Data from each patient was analyzed in 16 myocardial segments. STATISTICAL TESTS: The segment-wise T1 and T2 data were analyzed over time after surgery using linear mixed models for repeated measures analysis. RESULTS: The results showed that T1 relaxation times were significantly (P < 0.05) shorter 3 and 12 months postoperative than preoperative and that the T2 relaxation times were significantly (P < 0.05) longer 3 and 12 months postoperative than preoperative for both 3D and 2D mapping methods. No significant changes were seen between 3 and 12 months postoperative for any of the methods (P = 0.06/0.19 for T1 with 3D-QALAS/MOLLI and P = 0.09/0.25 for T2 with 3D-QALAS/GraSE). DATA CONCLUSION: We demonstrated that changes in myocardial relaxation times and thus tissue characteristics can be observed within 3 months after AVR surgery. The significant changes in relaxation times from preoperative examinations to the follow-up may be interpreted as a reduction of interstitial fibrosis in the left ventricular wall. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018.

Clinical feasibility of 3D-QALAS - Single breath-hold 3D myocardial T1- and T2-mapping.

PURPOSE: To investigate the in-vivo precision and clinical feasibility of 3D-QALAS - a novel method for simultaneous three-dimensional myocardial T1- and T2-mapping. METHODS: Ten healthy subjects and 23 patients with different cardiac pathologies underwent cardiovascular 3T MRI examinations including 3D-QALAS, MOLLI and T2-GraSE acquisitions. Precision was investigated in the healthy subjects between independent scans, between dependent scans and as standard deviation of consecutive scans. Clinical feasibility of 3D-QALAS was investigated for native and contrast enhanced myocardium in patients. Data were analyzed using mean value and 95% confidence interval, Pearson correlation, Paired t-tests, intraclass correlation and Bland-Altman analysis. RESULTS: Average myocardial relaxation time values and SD from eight repeated acquisitions within the group of healthy subjects were 1178±18.5ms (1.6%) for T1 with 3D-QALAS, 52.7±1.2ms (2.3%) for T2 with 3D-QALAS, 1145±10.0ms (0.9%) for T1 with MOLLI and 49.2±0.8ms (1.6%) for T2 with GraSE. Myocardial T1 and T2 relaxation times obtained with 3D-QALAS correlated very well with reference methods; MOLLI for T1 (r=0.994) and T2-GraSE for T2 (r=0.818) in the 23 patients. Average native/post-contrast myocardial T1 values from the patients were 1166.2ms/411.8ms for 3D-QALAS and 1174.4ms/438.9ms for MOLLI. Average native myocardial T2 values from the patients were 53.2ms for 3D-QALAS and 54.4ms for T2-GraSE. CONCLUSIONS: Repeated independent and dependent scans together with the intra-scan repeatability, demonstrated all a very good precision for the 3D-QALAS method in healthy volunteers. This study shows that 3D T1 and T2 mapping in the left ventricle is feasible in one breath hold for patients with different cardiac pathologies using 3D-QALAS.

Simultaneous three-dimensional myocardial T1 and T2 mapping in one breath hold with 3D-QALAS.

BACKGROUND: Quantification of the longitudinal- and transverse relaxation time in the myocardium has shown to provide important information in cardiac diagnostics. Methods for cardiac relaxation time mapping generally demand a long breath hold to measure either T1 or T2 in a single 2D slice. In this paper we present and evaluate a novel method for 3D interleaved T1 and T2 mapping of the whole left ventricular myocardium within a single breath hold of 15 heartbeats. METHODS: The 3D-QALAS (3D-quantification using an interleaved Look-Locker acquisition sequence with T2 preparation pulse) is based on a 3D spoiled Turbo Field Echo sequence using inversion recovery with interleaved T2 preparation. Quantification of both T1 and T2 in a volume of 13 slices with a resolution of 2.0x2.0x6.0 mm is obtained from five measurements by using simulations of the longitudinal magnetizations Mz. This acquisition scheme is repeated three times to sample k-space. The method was evaluated both in-vitro (validated against Inversion Recovery and Multi Echo) and in-vivo (validated against MOLLI and Dual Echo). RESULTS: In-vitro, a strong relation was found between 3D-QALAS and Inversion Recovery (R = 0.998; N = 10; p < 0.01) and between 3D-QALAS and Multi Echo (R = 0.996; N = 10; p < 0.01). The 3D-QALAS method showed no dependence on e.g. heart rate in the interval of 40-120 bpm. In healthy myocardium, the mean T1 value was 1083 ± 43 ms (mean ± SD) for 3D-QALAS and 1089 ± 54 ms for MOLLI, while the mean T2 value was 50.4 ± 3.6 ms 3D-QALAS and 50.3 ± 3.5 ms for Dual Echo. No significant difference in in-vivo relaxation times was found between 3D-QALAS and MOLLI (N = 10; p = 0.65) respectively 3D-QALAS and Dual Echo (N = 10; p = 0.925) for the ten healthy volunteers. CONCLUSIONS: The 3D-QALAS method has demonstrated good accuracy and intra-scan variability both in-vitro and in-vivo. It allows rapid acquisition and provides quantitative information of both T1 and T2 relaxation times in the same scan with full coverage of the left ventricle, enabling clinical application in a broader spectrum of cardiac disorders.